Synthesis and biological evaluation of positron emission tomography radiotracers targeting serotonin 4 receptors in brain: [F-18]MNI-698 and [F-18]MNI-699

Fabien Caille, Thomas J. Morley, Adriana Alexandre S. Tavares, Caroline Papin, Nicole M. Twardy, David Alagille, H. Sharon Lee, Ronald M. Baldwin, John P. Seibyl, Olivier Barret, Gilles D. Tamagnan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Two new benzodioxane derivatives were synthesized as candidates to image the serotonin 4 receptors by positron emission tomography (PET) and radiolabeled with fluorine-18 via a two-step procedure. Competition binding assays demonstrated that MNI-698 and MNI-699 had sub-nanomolar binding affinities against rat striatal 5-HT4 receptors (Ki of 0.20 and 0.07 nM, respectively). PET imaging in rhesus monkey showed that the regional brain distribution of [F-18] MNI-698 and [F-18] MNI-699 were consistent with the known densities of 5-HT4 in brain. [F-18] MNI-698 and [F-18] MNI-699 are among the first fluorine-18 radiotracers developed for imaging the 5-HT4 receptors in vivo and are currently under preclinical investigation in primates for future human use. (C) 2013 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)6243-6247
Number of pages5
JournalBioorganic & Medicinal Chemistry Letters
Volume23
Issue number23
DOIs
Publication statusPublished - 1 Dec 2013

Keywords

  • PET imaging
  • 5-HT4
  • Serotonin receptors
  • Fluorine-18
  • Alzheimer's disease
  • POSTMORTEM HUMAN BRAIN
  • 5-HT4 RECEPTORS
  • GUINEA-PIG
  • IN-VIVO
  • SELECTIVE RADIOLIGAND
  • HIGHLY POTENT
  • BINDING
  • ANTAGONIST
  • SB-207710
  • LIGAND

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